Activity-dependent refinement of visual circuitry

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The developing nervous system is able to achieve the remarkable precision of wiring found in the adult brain through a combination of molecular guidance cues and activity-dependent fine-tuning of connections. Much of the research on connection refinement in the past has focused on structural or synaptic changes that occur at the level of individual neurons and their axonal projections onto postsynaptic dendritic targets. In fact, to appreciate how the nervous system optimizes connectivity during development, it is necessary to study not just the activity-dependent remodeling of individual neurons, but rather the interactions between ensembles of neurons in response to patterned activity. This research program combines innovative live imaging techniques to study axonal remodeling of groups of neurons at single-cell resolution over time in vivo along with electrophysiological analyses of receptive field development to begin to dissect the complex interactions carried out by developing neurons to produce functional circuits. Our short-term goals are to develop and apply these new approaches to solving the fundamental, yet remarkably unanswered, question of how correlated neural activity instructively (as opposed to permissively) guides connection refinement in an NMDAR-dependent manner. This work will lay an important foundation for our long-term goals of carrying out a genetic dissection of the molecular signaling pathways that underlie instructive activity-dependent processes in development.